Dicarboxylic acids (diacids) are important compounds that are used in the manufacture of commercial polymers (e.g. polyesters, polyurethanes). The use of hybrid polyketide synthases to produce diacids having a carbon backbone with an odd number of carbon atoms is disclosed in International Patent Application Publication No. WO 2009/121066. However, commercial polymers are typically produced from reactants derived from petroleum and petrochemicals.
For example, as illustrated in FIG. 1, the dicarboxylic acid adipic acid [1] is used mainly as a monomer in the production of nylon 6,6 [2], a polyamide generated through the reaction of [1] with hexane-1,6-diamine. Polyesters (for use in fabrics and plastics of many compositions) are formed through the polymerization of terephthalic acid [3] and a dialcohol (diol) such as ethylene glycol (to make polyethylene terephthalate [4]), propane diol (poly(1,3-propanediol terephthalate) [5]) or butanediol (poly(1,4-butanediolphthalate) [6]. Adipic acid is also used in the synthesis of various polyesters. Currently adipic acid is synthesized via oxidation of cyclohexane and similar petrochemicals using traditional chemical synthesis.
Lactams are important compounds useful in the manufacture of a variety of compounds, including commercial polymers, particularly polyamides such as Nylon 6 and Nylon 12. Caprolactam is the sole source of Nylon 6, which is used in the production of durable fibers for carpets and in other products. Larger chain lactams, such as Nylon 12, are used in engineering plastics where their physical properties make them more desirable. The open chain form of these molecules are also accessible using the technology described herein. These cognate acids are also used in many of the same applications. For example, 6-aminohexanoic acid is the open chain form of caprolactam and can also be polymerized to produce Nylon 6.
Diamines are used extensively in the production of polymers, predominantly Nylons, as described above.
The large scale worldwide use of nylons and polyesters requires the production of millions of metric tons of adipic acid, caprolactam and 1,6-hexanediamine annually. The diacids, lactams, and diamines are themselves synthesized from starting materials extracted from petroleum. There is a need for new methods to synthesize such compounds in a manner that reduces dependence on oil.
Complex polyketides comprise a large class of natural products that are synthesized in bacteria (mainly members actinomycete family; e.g. Streptomyces), fungi and plants. Polyketides form the aglycone component of a large number of clinically important drugs, such as antibiotics (e.g. erythromycin, tylosin), antifungal agents (e.g. nystatin), anticancer agents (e.g. epothilone), immunosuppressives (e.g. rapamycin), etc. Though these compounds do not resemble each other either in their structure or their mode of action, they share a common basis for their biosynthesis, which is carried out by a group of enzymes designated polyketide synthases. Polyketide synthases (PKS) employ short chain fatty acyl CoAs in Claisen condensation reactions to produce polyketides. Unlike fatty acid synthases, which utilize acetyl CoA as the starter and malonyl CoA as the extender units and which use a single module iteratively to produce the nascent acyl chains, PKSs are composed of multiple, discrete modules, each catalyzing the chain growth of a single step. The present invention provides methods and compositions for employing polyketide synthases to produce diacids, lactams, diamines, e.g., for the production of commercial polymers.